Levofloxacin rescues mice from lethal intra-nasal infections with virulent Francisella tularensis and induces immunity and production of protective antibody.
The ability to protect mice against respiratory infections with virulent Francisella tularensis has been problematic and the role of antibody-versus-cell-mediated immunity controversial. In this study, we tested the hypothesis that protective immunity can develop in mice that were given antibiotic therapy following infection via the respiratory tract with F. tularensis SCHU S4. We show that mice infected with a lethal dose of SCHU S4, via an intra-nasal challenge, could be protected with levofloxacin treatment. This protection was evident even when levofloxacin treatment was delayed 72h post-infection. At early time points after levofloxacin treatment, significant numbers of bacteria could be recovered from the lungs and spleens of mice, which was followed by a dramatic disappearance of bacteria from these tissues. Mice successfully treated with levofloxacin were later shown to be almost completely resistant to re-challenge with SCHU S4 by the intra-nasal route. Serum antibody appeared to play an important role in this immunity. Normal mice, when given sera from animals protected by levofloxacin treatment, were solidly protected from a lethal intra-nasal challenge with SCHU S4. The protective antiserum contained high titers of SCHU S4-specific IgG2a, indicating that a strong Th1 response was induced following levofloxacin treatment. Thus, this study describes a potentially valuable animal model for furthering our understanding of respiratory tularemia and provides suggestive evidence that antibody can protect against respiratory infections with virulent F. tularensis.
Klimpel
Gary R
GR
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1070, USA. gklimpel@utmb.edu
Eaves-Pyles
Tonyia
T
Moen
Scott T
ST
Taormina
Joanna
J
Peterson
Johnny W
JW
Chopra
Ashok K
AK
Niesel
David W
DW
Carness
Paige
P
Haithcoat
Judith L
JL
Kirtley
Michelle
M
Nasr
Abdelhakim Ben
AB
D000281:Administration, Intranasal; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000907:Antibodies, Bacterial / Q000032:analysis / Q000096:biosynthesis*; D000917:Antibody Formation / Q000276:immunology; D015169:Colony Count, Microbial; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005604:Francisella tularensis / Q000472:pathogenicity; D064704:Levofloxacin; D051379:Mice; D008807:Mice, Inbred BALB C; D015242:Ofloxacin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016019:Survival Analysis; D014406:Tularemia / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D014774:Virulence; D015047:Zoonoses / Q000382:microbiology
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D064704:Levofloxacin; D015242:Ofloxacin